This Program Project brings together, links, and interdigitates six projects that over the range from the pattern of deposition of ionizing radiation, to early chemical events, to the earliest observable biological effects of radiation cytogenetics), to the late effects of radiation of concern in radiation protection mutation and oncogenic transformation). The projects each address the central theme of "The Effects of Small Doses of Radiation" from different points of view. The pattern of the deposition of energy will be measured in simulated volumes of biological significance, in what has come to be known as microdosimetry. Attention will focus on attempts to simulate smaller volumes of the order of nanometers. Theoretical research will include charged and uncharged Particle transport in condensed media and the subsequent stochastic treatment of radical diffusion and interactions. It will thus cover the first microsecond following the energy deposition event; this time interval is considered to contain, in terms of radiation quality, the "signature" of the field. The earliest observable biological effect of radiation is the production of chromosome aberrations and their production by a variety of types of radiation will be studied. Assays for oncogenic transformation represent a powerful tool and will be used or pragmatic studies involving the supra-additive interaction of radiation with chemical and physical carcinogens, as well as the study of chemicals and hormones that modulate transformation incidence. Mechanistic studies will be designed to identify and characterize the molecular changes that lead to the induction of malignancy. The project to produce a rational, empirical basis for quality factors is an excellent example of the collaborative and interdisciplinary research which characterizes this program project. Here, correlated measurements of both microdosimetric spectra and biological response are made and unfolded to produce the data needed to estimate quality factors. The underlying theme is the conviction that the biological effects of radiation can ultimately be explained and described in terms of physics and chemistry.